How to Improve CognitionPart I.I have been reading more about ways to improve cognition. I started with the fact that my son (and only he in my family) has a mutation in D-amino acid oxidase (DAO) activator (rs701567 TT), which makes DAO overactive, thus reducing D Serine, which is a co-agonist at NMDA receptors. This mutation has been associated with schizophrenia. Multiple papers report that brains of schizophrenic patients show reduced levels of D Serine and overexpression of DAO. Low activity of NMDA receptors is now a leading theory of schizophrenia.

NMDA receptors is a very touchy and controversial area. On one hand, NMDA activity is responsible for memory and learning. On the other hand, overstimulation of NMDA receptors causes seizures and neuron death (neurotoxicity). Glutamate is the main excitatory neurotransmitter that agonizes these receptors. Anything that reduces NMDA activity either through blocking them or through reducing glutamate has been called "neuroprotective". Neuroprotection has been the focus of biomed therapies for autism. There are several theories why neuroprotection is needed for autism. First, many autistic children have abnormal EEG activity or seizures, which affect learning and language. Second, high glutamate and overstimulation of NMDA receptors is often a result of brain inflammation (encephalopathy), which is now a leading theory of autism causes. So, it is hard to debate that NMDA receptors must be protected from overstimualtion. Especially in my son's case because he had abnormal EEG until we started him on Lamictal (reduces pre-synaptic glutamate release), which normalized his EEG and improved him socially. However, while reducing NMDA activity improves the social aspect of ASD, it appears to play the opposite role in cognition. Many anti-seizure meds (especially Valproic acid) are known for their cognitive side effects. Then there is a mounting evidence that negative symptoms of schizophrenia (cognition) are caused by low activity of NMDA receptors. Scientists are now studying new drugs for schizophrenia which are aimed at increasing NMDA activity through glycine co-agonist site. I have noticed that many "neuroprotective" substances carry a warning of worsening schizophrenia symptoms. So, which way to go from here?

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How to Improve CognitionPart II.OK. Glutamate is bad, and everybody agrees on that even those seeking a treatment for schizophrenia. Let's focus on glycine site. Basically, NMDA receptor requires two things for it to open (two keys if you wish): glutamate and glycine (or D-serine). Once the receptor is open, calcium ions flow into the neuron, making it to fire, which then leads to synaptic plasticity nd learning. Without firing there is no learning. Adding glycine as a supplement is one of the simplest ways to activate NMDA receptors, only it requires large doses (10-60g). Interestingly, and I still don't completely understand why, supplementing glycine at these doses doesn't cause neural overstimulation or seizures. In fact, glycine was reported to reduce seizures at doses 200mg/kg. Glycine also acts as an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. D serine has much higher affinity to the co-agonist site of NMDA receptors than glycine, which is why you only need 30mg/kg. The effect of D serine on neurotixicity and seizures is controversial. Some papers report that D serine potentiates anti-seizure med action. But some say that high levels of D serine cause seizures. In fact, Alzheimers patients have higher levels of D serine than normal.

Then there is Sarcosine, which is synthesized in our bodies and is present in many foods. It indirectly increases glycine by blocking its transport. "Early evidence suggests that intake of 2 g/day sarcosine as add-on therapy to certain antipsychotics (not clozapine) in schizophrenia gives significant additional reductions in both positive and negative symptomatology as well as the neurocognitive and general psychopathological symptoms that are common to the illness." At these relevant doses, sarcosine has shown no effect on seizure threshold. At high doses (1g/kg) it was shown to actually increase the seizure threshold. Sarcosine was studied on children with ADHD at doses 30mg/kg/day and showed marginally better performance mostly for oppositional defiance. I have been giving Sarcosine to my son for about 1 month at 500mg/day and saw no effects.

Finally, I get to Kynurenic acid, a product of the normal metabolism of amino acid L-tryptophan. KYNA acts as antagonist at the glycine-site of NMDA receptors. Because of that, it is considered "neuroprotective", and most internet resources will talk about how to increase Kynurenic acid rather than reduce it. However, as an antagonist of both NMDA and nicotinic α7 acetylcholine receptors, it negatively affects learning and memory. Those looking for treatments of negative symptoms of schizophrenia, are interested to find how to reduce Kynurenic acid. BCAA (specifically Leucine and Isoleucine) were found to reduce KYNA formation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318830/). One would expect an improvement in cognition from BCAA. But on the flip side, BCAA could be neurotoxic and lead to ALS according to one theory (https://www.ncbi.nlm.nih.gov/pubmed/19763733).

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How to Improve CognitionPart IIIThe following article lists many cognition enhancing drugs: https://www.omicsonline.org/open-access/neuroenhancement-in-healthy-adults-part-i-pharmaceutical-cognitiveenhancement-a-systematic-review-2155-9627-1000213.php?aid=51586. My attention got attracted by the following statement: "Serotonin is found to be involved in many physiological or pathophysiological processes including cognitive function. A large body of evidence indicates the interplay between serotonergic transmission and other neurotransmitters including acetylcholine, dopamine, γ-aminobutyric acid (GABA) and glutamate, in the neurobiological control of learning and memory". Ampakines (positive modulators of AMPA-glutamate receptors such as Piracetam) also seem very interesting. "Some members of the ampakine family of drugs may also increase levels of trophic factors such as brain-derived neurotrophic factor (BDNF)". Researchers have found that BDNF expression in particular is mostly induced by low doses of ampakines for short treatment durations. Some SSRI's like Prozac and Zoloft are claimed to increase BDNF too and promote growth of new neurons (neurogenesis). This is because SSRI's reduce stress and anxiety, which apparently attenuate BDNF and negatively affect brain development.

BDNF acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses. In the brain, it is active in the hippocampus, cortex, and basal forebrain - areas vital to learning, memory, and higher thinking. BDNF itself is important for long-term memory. Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells in a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active. Recently BDNF has been implicated in many disorders like depression and OCD. With depression, BDNF production is slowed down and eventually halted corresponding with severity. BDNF can be activated by healthy activities like exercise, social interactions, meditation, etc. BDNF is also activated during brain injury (cerebral ischemia, etc), to repair injured cells. In my opinion, increasing BDNF is probably the most important cognition enhancing therapy, which can create lasting effects. Here are things that can increase BDNF:

It is interesting that most of these supplements reduce anxiety and depression. So far, I have tried Quercetin, Bacopa, Curcumin, zinc, and niacin from this list. Quercetin had the most pronounced effect on my son by making him more aware and talkative. It is in my "hall of fame" because not only it reduces stress hormone and increases BDNF, but also because it stabilizes mast cells. Bacopa gave very weak effect by slightly improving the mood. I stopped it after a few months and saw no ill effects. Curcumin and zinc increased irritability in my son. I never saw any effects from niacin. EGCG is very similar to Quercetin: it also regulate adrenocorticotrophic hormone (ACTH) serum levels, inhibits of prostaglandins and inflammatory cytokines, stabilizes mast cells, and boost BDNF. EGCG, Resveratrol, and Baicalin (Baikal skullcap) are all worth trying next.

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I'm very interested in this research because I have both homozygous mutations in NMDA receptors and BDNF. Here are my points: Part I and II.NMDA receptors dysfunction I think increase Glutamate? The effects of NMDA-receptor antagonists in animal models have shown a significant increase in glutamate release, possibly because the body is attempting to compensate for reduced signaling by releasing more of the messenger [Moghaddam and Jackson, 2003].If it was the opposite, then any activator has to be taken with caution. what about taking something control Glutamate while on NMDA activator? Like Taurine or NAC?Apart from Glutamate, the overactive of NMDA wouldn't be a good idea I guess.

Part III. I have this recommendation for BDNF mutation:Theanine, Curcumin, Beta-alanine, Lithiumorotate, Phosphatidylserin. I tried Theanine, Curcumin and PS. I noticed some results from PS but it gave me a headache. From your list

I tried Quercetin, Niacin, Zinc, Rhodiola, Bacopa, and Acupuncture I noticed a good result only from Rhodiola but stopped it since it is very effective especially on Dopamine and I have different genes mutations regarding Dopamine so I would avoid anything that may interact with it. Also I was having racing thoughts recently so I may get schizoaffective disorders. There is an interested study about BDNF and Taurine https://www.ncbi.nlm.nih.gov/pubmed/25612506

Also Lion mane's Mushroom seems effective https://www.ncbi.nlm.nih.gov/pubmed/24266378I haven't tried any of them yet. I gave my mother Taurine for a good sleep and it is really helping her and she is actually happier now. What really helped my cognition in the past was Sulforaphane and Pycnogenol( only one brand of Pycnogenol from Holland and Barrett, the other brands didn't work at all). It may stimulates BDNF, I'm not sure.

Marya wrote:I noticed a good result only from Rhodiola but stopped it since it is very effective especially on Dopamine and I have different genes mutations regarding Dopamine so I would avoid anything that may interact with it. Also I was having racing thoughts recently so I may get schizoaffective disorders.

Thanks, Marya, for sharing your experience. I found that other people reported worsening psychotic symptoms on Rhodiola. I still don't know where my son falls on the spectrum ADHD - Autism - Schizophrenia. If he is closer to ADHD, then increasing dopamine with Rhodiola might be a good idea. My psychiatrist kept recommending me to start my son on an ADHD stimulant drug saying that only these drugs were shown clinically to improve focus, learning and cognition. The rest is just "beating around the bush". He said that at small doses, these drugs rarely cause any psychotic problems. But I want to be safe. I will remove Rhodiola from my list. There are other things that can increase BDNF such as EGCG and Resveratrol. Have you ever tried Resveratrol? There was a member in his 50's here, who had depression and anxiety, I believe. He claimed Reservatrol helped him a lot, but he was still searching for other solutions. His username name is AspieGenes. He was into genetic analysis and was offering some of us here to look at our genes and compare them to his list. Try to contact him.

Marya wrote:I noticed a good result only from Rhodiola but stopped it since it is very effective especially on Dopamine and I have different genes mutations regarding Dopamine so I would avoid anything that may interact with it. Also I was having racing thoughts recently so I may get schizoaffective disorders.

Thanks, Marya, for sharing your experience. I found that other people reported worsening psychotic symptoms on Rhodiola. I still don't know where my son falls on the spectrum ADHD - Autism - Schizophrenia. If he is closer to ADHD, then increasing dopamine with Rhodiola might be a good idea. My psychiatrist kept recommending me to start my son on an ADHD stimulant drug saying that only these drugs were shown clinically to improve focus, learning and cognition. The rest is just "beating around the bush". He said that at small doses, these drugs rarely cause any psychotic problems. But I want to be safe. I will remove Rhodiola from my list. There are other things that can increase BDNF such as EGCG and Resveratrol. Have you ever tried Resveratrol? There was a member in his 50's here, who had depression and anxiety, I believe. He claimed Reservatrol helped him a lot, but he was still searching for other solutions. His username name is AspieGenes. He was into genetic analysis and was offering some of us here to look at our genes and compare them to his list. Try to contact him.

Rhodiola is very good for focus and attention. If your son has ADHA it may work well for him. I think if the attention disorder comes from Dopamine low level then Rhodiola would work well with L-tyrosine. But if the attention disorder comes from NMDA dysfunction or BDNF or unbalance of Glutamate/GABA then other supplements could be worth trying. Schizophrenics' Dopamine level is very high that what cause them most of the symptoms, also they would sever from lack of attention and cognitive issue but imagine if they take any ADHD drug for their cognitive what would happen to their brain. My brother is Schizo and when he wants to boost his cognition with energy drink like Redbull he gets very bad headache and that worse his symptoms. Thanks for letting me know about the man, I would try to contact him.I haven't actually tried Resveratrol but I may try it soon. I have got Lion's mane mushroom and I want to give it a try, it seems effective. Any thought about it? Also would try Taurine for BDNF. And will update hopefully with good results.

Marya wrote:I have got Lion's mane mushroom and I want to give it a try, it seems effective. Any thought about it? Also would try Taurine for BDNF. And will update hopefully with good results.

Taurine is in my "hall of fame". I have been giving it to my son for sleep for over 3 years. Lion's Mane is supposed to be great for cognition, activates NGF, recommended for brain injuries. I even bought some for my son but haven't tried yet. I will wait until you report your experience with it. Have you tried cocoa? I know you are staying away from Dopamine, and cocoa contains phenylalanine, which will boost Dopamine. But it has so many good things about it: antioxidant, neuroprotective, stimulates cerebral blood flow, stimulates NGF, etc. Cocoa powder is quite cheap too (or eat dark chocolate, but it has too much fat and sugar). I drink cacao in the afternoon to boost my mental power. It really helps me. But my wife gets cranky on chocolate. I suspect that my son will also get cranky, but one day I will try it anyway.

Could you explain your problems with cognition? You mentioned that it is different from ADHD. My psychiatrist explained that ADHD is present when a patient can't concentrate on a task and finish it because of mental fog, has day dreams, lacks motivation. However, how one can tell a difference between lack of concentration due to a mental fog (slow processing) and lack of concentration due to racing thoughts? I dealt recently with a schizophrenic contractor who just couldn't finish the job because he wanted to talk about a topic of his obsession (video games). If I look at my son, he is more on the "slow processing" side rather than having too many things in his head. He has a bored look, yawns, almost falls asleep every time I do homework with him. I guess it is ADHD rather than schizophrenia. But, when he watches his favorite videos or plays on iPad, he is extremely excited, flaps his hands, very hyperactive just like that schizophrenic contractor.

Could you explain your problems with cognition? You mentioned that it is different from ADHD. My psychiatrist explained that ADHD is present when a patient can't concentrate on a task and finish it because of mental fog, has day dreams, lacks motivation. However, how one can tell a difference between lack of concentration due to a mental fog (slow processing) and lack of concentration due to racing thoughts? I dealt recently with a schizophrenic contractor who just couldn't finish the job because he wanted to talk about a topic of his obsession (video games). If I look at my son, he is more on the "slow processing" side rather than having too many things in his head. He has a bored look, yawns, almost falls asleep every time I do homework with him. I guess it is ADHD rather than schizophrenia. But, when he watches his favorite videos or plays on iPad, he is extremely excited, flaps his hands, very hyperactive just like that schizophrenic contractor.

I haven't tried Cocoa. Thank you for sharing your experience. Will give it a try. My problem with cognition is actually different. I do hear but the words sometimes don't make sense to me or my brain doesn't analysis them. So the attention is actually there but doesn't help me. And sometimes when I get them I don't analysis or judge the situations properly. On the other hand I do well with the written words, so I prefer to contact people via messages. However, now I'm doing better than before especially when I started taking MSM ( I started to hear, see, feel, sense like normal people) I'm now back to take MSM, just 3 days ago but still haven't got the benefits. My attention can be poor sometimes when I'm stressed out. I do daydreams but because I don't live my life fully but when I feel well I'm always in the present. My brother is better than me in cognition but he suffer from a little of hallucinations(voices). He also get excited when he does what he likes and read a lot on books he likes but very slow at School. He has a solid knowledge about random subjects, Economy, politics, history, art, media and medicine!! But he never finished any degree! I remember that he was similar to your son, fell asleep when he used to do his homework. Have you tried Inluin protocol? I have started taking it last week. I also gave it to my brother. Thank you so much for the link. It is well researched.

Marya, based on your description of your brother, he sounds similar to my son. I'd better off staying away from dopamine. I just learned from another blog that some farther is giving his autistic son Agmatine Sulfate, a nitric oxide booster, and is seeing great effect on cognition and language. I just ordered some for my son after reading many good things about it (good summary is here https://www.powdercity.com/products/agmatine-sulfate). It is the stuff that is produced inside of our bodies from Arginine. It is stored in neurons and released together with glutamate. But, as opposed to glutamate, it is a weak antagonist of NMDA receptors, and as such is neuroprotective and calming. https://www.ncbi.nlm.nih.gov/pubmed/27638451 "a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model [of autism]". Hopefully it will rescue my son from stims . Agmantine is 100x more potent at increasing brain circulation. It is used primarily by bodybuilders. It is interesting how I am finding these cognition enhancing substances (Creatine and now Agmatine) in bodybuilders stacks.

As far as Inulin is concerned, I have been giving it to my son together with Krill Oil for about 4 months. It helped my son to be calmer, much less aggressive.

FatherOf2 wrote:Marya, based on your description of your brother, he sounds similar to my son. I'd better off staying away from dopamine. I just learned from another blog that some farther is giving his autistic son Agmatine Sulfate, a nitric oxide booster, and is seeing great effect on cognition and language. I just ordered some for my son after reading many good things about it (good summary is here https://www.powdercity.com/products/agmatine-sulfate)

Wow that's awesome! I would give it a try. But what about increasing norepinephrine/noradrenaline? Would it be harmful for any Panic attack patient?It is said that it modulate NMDA receptors, by reducing the function of it, right? Because you said it is a weak antagonist. I would recommend you to try Lion's Mane mushroom first, as it doesn't affect neurotransmitters but rather it stimulates nerves growth. It is even more safe than Curcumin. Have you tried anything to boost Glutathione Peroxidase and reduce oxidative stress? By the way, does the activation of NMDA receptors reduce or increase Glutamate?

Users report reduced anxiety. However, according to that farther of the autistic boy taking Agmatine, "there seem to be an adjustment period the first couple of days with some agitation". I don't know what does agitation mean in this cases. I wouldn't expect hyperactivity from something that inhibits NMDA receptors. He further reports that it took him a while to find the right dose of 22.2mg/kg per day. In literature, the recommended dose is 1-2g.day, and I was planning to start at 200-300mg to be on the safe side.

Activation of NMDA receptors is unpredictable, so is their inhibition. There are feedbacks in the brain that adjust things to maintain the signal constant. For example, I have read somewhere that an inhibition of NMDA receptors may increase their number. I would expect an opposite action from their activation, i.e. reduces number of receptors. But I am not sure if glutamate gets modulated too. These feedbacks are the reason why most receptor modulating drugs fail to maintain their action long term and require increasing doses or cycling.

How to boost Glutathion Peroxidase? Anything I tried to modulate Glutathione (Curcumin, AL, NAC, DMSA, DMPS) ended up increasing my son's irritability probably because they all contained sulphur, which my son reacts negatively. That reminds me that Agmatine is sulfate. So, I have to be careful with it.

Thank you Fatherof2 for your post. I think I will try Agmatine soon since I need to boost my cognition and attention to finish my studies Regarding NMDA activation, if I try Sarcosine I think will I have to be careful and take NAC or Taurine to control Gultamate. There are a lot of studies on NAC and how it significantly reduce Glutamate and that made it a good treatment for Schizophrenia and other disorders. I think will give it to my brother. That's why I saw that Schizophrenics commented on their site that NAC was given them good results even without Sarcosine. Have you tried Sarcosine with any Glutamate modulator?

In relation to Glutathione Peroxidase, I recommend you to try Pycnogenol, they are some studies on it that it may raise glutathione significantly within 1 month. I know you already tried it but maybe switch to another brand. I tried one from Holland and Barrett, and it worked very well and even my skin was very bright. But it was expensive and I ordered one from iherb, I think from healthy origin, but haven't seen any result.

I started to feel that I get irritable when I take Sulphur but I really needs it, so I was thinking today to take any calmer supplement, like Magnesium. Taurine may be good enough but I don't want to fell asleep during the day. I will try Magnesium and will update you if I notice anything.

Sarcosine is not doing anything in my son. He is already taking glutamate reducing drug, Lamictal, for his EEG. I think that increasing co-agonist (glycine) concentration by Sarcosine doesn't work unless there is enough agonist (glutamate). Remember that you need glutamate AND glycine to activate NMDA receptors. I have read those posts by schizophrenic patients. Most effect was reported with NAC but not Sarcosine. I will stop Sarcosine when I start trial of Agmatine. EGCG (green tea extract) also comes up a winner on many of my screens.

I tried Pycnogenol multiple times in the last 4 years. It didn't work for my son at all, at any dose (50mg or 100mg), 2-3 different bands; regardless how long he took it. I am putting this one into "useless" list for good.

I've found thisGlycine is also a special case neurotransmitter. If the balance in your body is towards glutamate, glycine will be excitatory. If the balance is toward GABA, it will be inhibitory. So if you tend toward glutamate excess, avoid glycine.I think this is to be considered before taking Sarcosine.I do have mutations in the GAD enzyme that converts Glutamate to GABA so I assume that I have high Glutamate and low GABA.

Marya wrote:I've found thisGlycine is also a special case neurotransmitter. If the balance in your body is towards glutamate, glycine will be excitatory. If the balance is toward GABA, it will be inhibitory. So if you tend toward glutamate excess, avoid glycine.I think this is to be considered before taking Sarcosine.I do have mutations in the GAD enzyme that converts Glutamate to GABA so I assume that I have high Glutamate and low GABA.

Could you tell me the rsid number of your GAD mutation.

Also, to update. I received Agmatine on weekend and started trying it on myself before giving it to my son. I definetely noticed increased blood flow to brain, but no heafache like on Ginkgo. Whether that made me smarter remains to be seen. But, coincidentally or not, I started sleeping better and having vivid dreams (I usually sleep poorly, with several wakings during night, dream rarely).

I have homozygous in rs2241165 and heterozygous in rs3791850, rs3791851 and rs701492 They are all GAD1 and they came up on NutraHacker report. Agmatine sounds great. Will be next on my list. Please keep us updated.

Marya wrote:I have homozygous in rs2241165 and heterozygous in rs3791850, rs3791851 and rs701492 They are all GAD1 and they came up on NutraHacker report. Agmatine sounds great. Will be next on my list. Please keep us updated.

FatherOf2 wrote:Which letters do you have for rs2241165? My son is T/T.

For rs2241165 is CC so it was considered as homozygous. The others GAD1 are AG, CT, so they are heterozygous. I think your son is lucky so he doesn't have high glutamate and low GABA. Does he have any heterozygous for other GAD1 enzymes?

I think Glycine treatment should be fine for him. I'm still not fully understood NMDA activation and glutamate level though. Some people say glutamate would be under control when NMDARs activated and some say the opposite. On NutraHacker report they recommended Glycine for GAD1 mutation(High glutamate and low GABA) I'm very confused. The other recommendations are Taurine and NAC, Taurine to raise GABA and NAC to reduce glutamate.

He is homozygous on two GAD1 mutations:rs3749034 GG (even though it is a more common allele than other alleles)rs3828275 TTBasically, the first "mutation" is the same for about 70% population. And according to selfdecode, the Major "G" allele is associated with:- Reduced GAD1 production in the DLPFC and hippocampus among people with schizophrenia. The binding site for two transcription factors is disrupted.- Significant decrease in KCC2 (gene that helps GABA) production in the hippocampus (p < 0.004), compared with minor allele carriers.- Significant reduction of cortical thickness in the left parahippocampal gyrus (PHG).- Cortical thickness reductions of GG were only found in people with the COMT Val158Met versions of AG and GG, but not AA. Increased risk of schizophrenia.So, 70% of the world should be schizophrenic according to this write up. But since most people are not schizophrenic, it means that you need other mutations to increases the chances. But nobody yet knows what combo of mutations is critical. Besides, some mutations work in opposite ways. For instance, while my son has those two GAD1 mutations, which increase glutamate, he has a DAOA mutation which reduces D-serine, co-agonist of NMDA receptors. So, you should treat individual mutations with a grain of salt. The net effect of multiple mutations on NMDA receptors might be zero. In the end, it is all about trying different things and seeing what works.

By the way, after taking Agmatine for about a week at 250mg in the morning, I decided that I will not be giving it to my son. After about 2-3 days of feeling OK and having good sleep (probably coincidental), I went back to having sleepless nights. I started having an unpleasant feeling of heavy head and had a headache today. I felt like I became stupid in the last two days, forgetting simple things, and having trouble picking the right words. On the positive side, I felt less anxious and less emotional. I don't think Agmatine should be taken for more than 2-3 days in a row. I am slowly coming to a conclusion that increasing the brain circulation too much may not be an efficient way of improving cognition. Personally, my body prefers anti-inflammatories like Ibuprofen, which always makes me feel light and happy and willing to do many things. Cacao also revs up my brain without the unpleasant "heavy head" filling, even though it increases cortical blood flow in addition to being antioxidant. Again, reducing inflammation might be a key to cognition.

You are right about those mutations. So you beleive that NMDARs dysfunction reduce glutamate level? I do have one GAD1 homozygous, and 3 heterozygous. And one DAOA homozygous, and the other is heterozygous.

I'm sorry to hear about Agmatine and its side effects. Hope you feel better soon. It doesn't seem benefical at all. The anti inflammation benefits for cognition is good enough, I've tried MSM and it helps a lot with my cognition. Fish oil is also good for inflammation. I'm still taking inulin now for the second week and my gut feels better.

If you want to increase the blood circulation try 5mg of Vinpoctine, I've tried it and it is very light.

Also don't forget Lion's mane, I think it is very safe. I haven't tried it yet as I'm healing my gut and the inflammation, also boosting GABA.

Once the inflammations in my body is under the control and my gut is healed will definitely try it as I have BDNF mutation, and may help my neurons to grow better..hopefully